DESCRIPTION: Coronary heart disease remains one of the primary causes of morbidity and mortality in the U.S. Plasma lipid concentrations are strong predictors of the extent of disease. Dietary recommendations to optimize plasma lipid profiles include reductions of total dietary fat, saturated fat and cholesterol. However, individual responses to diet suggest that there is a strong genetic component to serum lipoprotein response to dietary manipulation. The P.I. and his research team, as well as other investigators, have shown that polymorphisms in several candidate genes related to lipid metabolism are associated with increased dietary response to intervention studies. These candidate genes include apoA-I, apoB, apoE and apoC-III and apoA-IV. The goals of this proposal are to: 1) determine the effects of nine genetic variants at six candidate gene loci on fasting plasma total, LDL, HDL-cholesterol and triglyceride concentrations in a free living population (Framingham Offspring, n=3,600 and OMNI, n=1,200 African-American and Hispanic Cohorts) and their modulation by dietary habits, age, gender and other environmental variables; and 2) determine the effect of genetic variability at these loci on individual plasma lipid changes resulting from modification of dietary habits in a free living population.